Speaking of Medicine

Porta C, Kotecha A, Burman A, Jackson T, Ren J, et al. (2013) Rational Engineering of Recombinant Picornavirus Capsids to Produce Safe, Protective Vaccine Antigen. PLoS Pathog 9(3): e1003255. doi:10.1371/journal.ppat.1003255

New articles publishing in PLOS NTDs this week:

The newly completed genome sequence of S. haematobium together with advanced genetic manipulation technologies are providing new insights that could lead to the development of the next generation of tools for eliminating this ancient scourge. Drs. Peter Hotez and Paul Brindley discuss the advances of the past two years towards a new era of S. haematobium research.

Ae. albopictus has expanded its range throughout the tropics and into some temperate regions in recent decades from its native South East Asia, carrying with it viruses including dengue and chikungunya. Dr. Marcus Blagrove and colleagues have conducted experiments with Ae. albopictus that show this vector, when trans-infected with Wolbachia, loses the ability to transmit dengue and chikungunya without any detectable fitness costs.

The Southern Chiapas focus of onchocerciasis in Mexico represents one of the major foci of this parasite in Latin America, but the absence of infective larvae in its black fly vector and reduction of exposure to new infections indicate that transmission has been interrupted. In this study, Dr. Rodriguez-Perez and colleagues present entomological and epidemiological assessments from this region to demonstrate interruption over this geographically large area.

New articles publishing in PLOS Pathogens this week:

KdpD/KdpE has recently been identified as an adaptive regulator involved in the virulence and intracellular survival of pathogenic bacteria. In this Review, Freeman and colleagues summarize evidence that KdpD/KdpE production is correlated with enhanced virulence and survival, that it regulates a range of virulence loci through direct promoter binding, and that its regulation responds to virulence-related conditions.

Foot-and-mouth disease remains a major plague of livestock, but current inactivated virus vaccines require expensive high containment facilities for their production and maintenance of a cold chain for their activity. Here, Porta and colleagues address both of these major drawbacks by developing methods to efficiently express recombinant empty capsids and enhancing capsid stability by incorporating a rationally designed mutation.

Despite the prevalence and severity of dengue virus (DENV), there are no approved vaccines or antiviral therapeutics available. In this paper, Morrison and colleagues demonstrate the requirement of a host factor, UBR4 a 600-kDa, for DENV to overcome the antiviral interferon response.  They suggest that this might be important for the design of specific DENV inhibitors that prevent the virus from evading innate immunity.

PLOS NTDs Editor-in-Chief, Peter Hotez, highlights the continuing disproportionate burden of neglected diseases and incarceration among African Americans.

In the United States of America, a higher percentage of African Americans live in poverty than any other racial/ethnic subgroup.  According to the U.S. Census Bureau, 27.4% of blacks lived below the poverty line in 2010, compared to 9.9% non-Hispanic whites, while 38.4% of black children (almost five million children) lived in poverty compared to 12.4% of non-Hispanic white children [1].  A high percentage of Hispanics (26.6%) and their children (35%) also live below the poverty line [1].

One of the more compelling reasons for this huge disparity among poverty levels was  stated recently by Michelle Alexander, a law school professor at Ohio State University.  In her landmark book, The New Jim Crow: Mass Incarceration in the Age of Colorblindness (The New Press), she makes a convincing case that the Jim Crow order that existed in this country prior to the 1960’s Civil Rights movement never really disappeared but instead was reincarnated in the form of incarcerating a generation of young African American men [2]. As Alexander states in her book, the 30-year-old “War on Drugs” has expanded the U.S. penal population almost 10-fold –from 300,000 to 2 million. Today the U.S has the largest number of prisoners anywhere in the world – even more than China or Iran [2].  Most of those are jailed for convictions of non-violent crime related to drug possession, and in some states black men are 20-50 times more likely to see prison time than white men [2]. In Washington, D.C., three of  four black men have or are at risk of serving time in prison [2].

To me, one of her most startling assertions is that the U.S. now sends a higher percentage of its black population to prison than South Africa did during the apartheid era [2].

Upon leaving prison, black men cannot escape the stigma of a felony conviction. They are often unable to find employment and support their families.  They are also denied the right to vote. Alexander asserts that this current situation has little to do with protecting the public welfare but everything to do with preserving a status quo of a racial caste system in America.

This disturbing data undoubtedly account for a significant amount of maternal and child poverty among African Americans in the U.S. Five years ago, I proposed a second possible underlying factor, namely high rates of neglected tropical diseases (NTDs) among the poor, especially in the American South [3]. NTDs are chronic infections often lasting for years that both occur in the setting of poverty and can actually cause poverty by making people too sick to go to work and causing developmental delays in childhood. My research published in a PLOS Neglected Tropical Diseases article entitled, “Neglected infections of poverty in the United States of America”, identified a (previously hidden) burden of NTDs among the poor in the U.S. and mostly among people of color [3]. The leading NTDs among African Americans include toxocariasis, a parasitic cause of asthma and epilepsy; trichomoniasis, a sexually-transmitted parasitic infection, congenital cytomegalovirus (CMV) infection that results in severe mental disabilities and deafness, congenital syphilis, and possibly dengue [3].   I estimated that the number of cases of these NTDs among African-Americans exceeds 4 million at any given time [3]. These are not rare diseases!  Among Hispanics, a second group of NTDs includes Chagas disease and cysticercosis [3].  I recommended a series of measures to combat NTDs in the U.S. including programs of active surveillance, disease transmission studies and research and development efforts to produce new drugs, diagnostics, and vaccines [3].

This summer will mark five years since the original publication of the PLOS article. Over this time period, I am afraid to say not very much has happened at the state or federal levels. Given our success in highlighting NTDs in developing countries so far it is profoundly disappointing to me that I have not achieved similar success in highlighting the impact of NTDs among the poor and disenfranchised in my own country. Even a modest piece of legislation with no funding entitled the Neglected Infections of Impoverished Americans Act has basically gone nowhere in the U.S. Congress.

Beginning in 2012 I began trying to resurrect interest in NTDs among people of color in the U.S. by writing high profile op-ed pieces in The New York Times, BMJ, and PLOS NTDs [4-6].   CNN’s Soledad O’Brien was amazing in giving air time to the issue.  These activities followed on the heels of my relocation to Houston, Texas, to establish a new National School of Tropical Medicine at Baylor College of Medicine [7], which has as a focus NTDs in the Americas, including those in Texas where the largest concentration of these diseases probably occurs.

Later this spring, the second edition of my book, Forgotten People, Forgotten Diseases: The Neglected Tropical Diseases and their Impact on Global Health and Development (ASM Press) will be published and will include updated chapters on NTDs in the U.S.  I’m hopeful the book together with a new foreword by Soledad O’Brien might help to re-energize interest in the problems of disease and poverty everywhere, but I am equally eager to see if it might finally call attention to the poor, underserved, and people of color in the USA.

Literature Cited
1.    http://www.npc.umich.edu/poverty/, accessed March 23, 2013.
2.    Alexander M.  2012. The New Jim Crow: Mass Incarceration in the Age of Colorblindness.   The New Press  312 p; pp 6-7.
3.    Hotez PJ. 2008. Neglected infections of poverty in the United States of America.  PLOS Negl Trop Dis  2: e256.  http://www.plosntds.org/article/info%3Adoi%2F10.1371%2Fjournal.pntd.0000256, accessed March 24, 2013.
4.    Hotez PJ. 2012. Fighting neglected tropical diseases in the southern United States.  BMJ  345: e6112. http://bakerinstitute.org/publications/HPF-pub-HotezBMJ-091312.pdf, accessed March 24, 2013.
5.    Hotez PJ. 2012. Tropical diseases: the new plague of poverty.  The New York Times , August 18, 2012. http://www.nytimes.com/2012/08/19/opinion/sunday/tropical-diseases-the-new-plague-of-poverty.html?_r=0, accessed March 24, 2013.
6.    Hotez PJ, Bottazzi ME, Dumonteil E, Valenzuela JG, Kamhawi S, Ortega J, Rosales SP, Cravioto MB, Tapia-Conyer R.  2012.  Texas and Mexico: sharing a legacy of poverty and neglected tropical diseases.  PLOS Negl Trop Dis  6: e1497.  http://www.plosntds.org/article/info%3Adoi%2F10.1371%2Fjournal.pntd.0001497, accessed March 24, 2013.
7.    http://www.bcm.edu/tropicalmedicine/, accessed March 24, 2013.

Demers J-P, Sgourakis NG, Gupta R, Loquet A, Giller K, et al. (2013) The Common Structural Architecture of Shigella flexneri and Salmonella typhimurium Type Three Secretion Needles. PLoS Pathog 9(3): e1003245. doi:10.1371/journal.ppat.1003245

New articles publishing in PLOS NTDs this week:

Dr. Donald Shepard and colleagues release two complimentary papers, one research article and one systematic review, highlighting the disease and economic burden of dengue on twelve nations in SE Asia. Quantifying dengue’s impact is a critical task that helps policy makers set priorities and make informed decision about disease control.

Prevention guidelines for melioidosis are hampered by a lack of evidence on which to base them. Dr. Limmathurotsakul and colleagues report on a matched case-control study that tested inoculation, inhalation and ingestion as possible routes of infection. With these results the team was able to develop the first evidence-based guidelines for the prevention of melioidosis.

New articles publishing in PLOS Pathogens this week:

Viewed from a neo-Darwinian perspective, the main function of the metazoan immune system (IS) is to insure host integrity against invading microorganisms. Coevolution of the host and the competitors has been described as a perpetual arms race. In this Opinion, Dr. Eric Muraille argues that observations from microbiology and ecology challenge this paradigm and suggests that infectious organisms and the IS play a crucial, unexpected role in evolution.

The reason for the severity of mucosal leishmaniasis is largely unknown. However it is known that the severe disease appears to be due to an uncontrolled inflammatory response that includes elevated production of IFN-c and IL-17. Dr. Gonzalez-Lombana and colleagues show that IL-17, but not the IFNc, is a strong candidate to be targeted in strategies to control the severe immunopathology observed in mucosal leishmaniasis patients.

The Type Three Secretion System (T3SS) is a macromolecular infection machinery present in many pathogenic Gram-negative bacteria such as Salmonella typhimurium and Shigella flexneri. Dr. Demers and colleagues show that Shigella subunits adopt the same secondary structure and orientation as in the atomic model of Salmonella, revealing a common structural architecture of T3SS needles, essential to understanding T3SS-mediated infection.

Since 2012, as well as being PLOS Medicine’s Chief Editor, I have combined that role with Medicine Editorial Director for PLOS – overseeing our three medical journals, PLOS Medicine, PLOS Pathogens and PLOS Neglected Tropical Diseases. I was one of the three editors that started PLOS Medicine and was its first Chief Editor; so, in one way or another, I have been closely involved in running the journal for the almost 10 years it has existed.

We have now decided to separate out the two roles — of Medicine Editorial Director for PLOS, and that of PLOS Medicine‘s Chief Editor — and later this year I will be therefore stepping down as Chief Editor. We have taken this decision for a number of reasons, once of which is personal, in that I am moving with my family to Australia.

I have been intimately connected with the journal from its very beginnings. Overseeing PLOS Medicine and working with colleagues on the journal has been the biggest and most rewarding challenge of my professional life. From the beginning, when PLOS Medicine set out to show that open-access publishing was compatible with the highest standards in medical publishing, we have filled a very specific niche in medical journal publishing – and have become a journal that, despite its size, regularly punches above its weight. Among our achievements, we have campaigned on important issues in medical publishing, prioritized for publication papers on the diseases and risk factors that cause the highest burden of disease, championed rigour in medical journal publishing, including better reporting of papers, and have rejected the conflicts that many journals have with the vested interests of the pharmaceutical and other industries. Along the way we have  published many great papers, but most importantly I believe have been a catalyst for change in a way that was, and still is, sorely needed in medical publishing.

I am very pleased I won’t be leaving PLOS altogether and will as Medicine Editorial Director remain able to champion PLOS Medicine and its values both inside and outside of PLOS. We are now recruiting for the new Chief Editor and I will remain in the post until they are recruited. The new editor will inherit not only a fantastic set of professional editors and journal staff, but also a tremendous, engaged academic editorial board that has really allowed us to become what we are now.I’m looking forward to seeing where the journal goes next. Oh, and of course representing PLOS in a new part of the world!